A commentary on ‘development and validation of safety and efficacy-associated risk calculator for hepatocellular carcinoma in the elderly after resection (searcher): a multi-institutional observational study’ (Int J Surg 2022;106:106842)
Authors: Teh-Ia Huo, Shu-Yein Ho, Jia-I Liao
Journal: International Journal of Surgery (2023)

Dear Editor, We read with interest the paper ‘Development and validation of safety and efficacy-associated risk calculator for hepatocellular carcinoma (HCC) in the elderly after resection (SEARCHER): a multi-institutional observational study’ published in a recent issue of International Journal of Surgery1. It is an elegant study that aimed to develop a predictive model for elderly patients with HCC undergoing surgical resection. Although the proposed SEARCHER is a feasible model, some drawbacks may deserve the authors’ attention. Firstly, in Chen et al.’s1 study, cancer-specific and overall survival are the two major primary end point for observation. However, since postresection tumor recurrence is quite common in HCC, most liver surgeons and liver cancer experts would agree that tumor recurrence may be a more suitable end point for surgical HCC. Consistent with the current study1, our previous work showed that 59% (308/522) of HCC patients developed tumor recurrence within 5 years of resection2. Therefore, tumor recurrence (or cancer-free survival) should also be included in the analysis to be more informative. This issue is critical because the forms of postrecurrence anticancer therapy might impact the long-term survival. Unfortunately, this information was not mentioned in Chen et al.’s study, and this could greatly limit its clinical applicability. Second, it is well known that microvascular invasion (MVI) is a major determinant for long-term survival in patients with HCC undergoing surgical treatment3,4. Importantly, the confirmation of MVI can only be demonstrated from the slice-cut resected specimen postoperatively. This is especially crucial when the prevalence rate of MVI was reported to reach 40.5% for tumor less than or equal to 2 cm and 49.6% for tumor 2.1–4 cm in diameter, respectively, in a surgical series of 322 patients3. The potentially high frequency of MVI in HCC is further supported by a classical study that looked at the explant livers in HCC patients undergoing liver transplantation, because tiny (less than 5 mm) satellite nodules were frequently identified in the explants through serially examining the slice-cut specimen5. Failure to include this variable in the analysis could miss the critical information linked with tumor recurrence and patient long-term survival. Third, the proposed SEARCHER model in Chen et al.’s6 study has not been adequately compared with the currently used staging systems for HCC in terms of prognostic prediction. Up to now, there are at least 11 staging systems for HCC. In addition, there are quite a few recently proposed staging models for HCC based on new biomarkers such as albumin-bilirubin grade and tumor burden score during the construction of either the predictive model or nomogram7,8. As such, all these models should undergo head-to-head comparison for outcome prediction. In summary, selection of the observational end point, detection of MVI, and the comparison with the currently used prognostic models are all critical issues for surgical HCC cohort. Providing accurate information is expected to play an important role in improving patient management and prognostic prediction. The predictive accuracy of the proposed RESEARCHER model for these patients remains to be seen. Ethical approval This paper is a letter correspondence and does not require ethical approval. Sources of funding This study was supported by a grant from Taipei Veterans General Hospital (VN111-07), Taiwan. Author contribution T.-H.H. and J.-I.L. performed the research. S.-Y.H. and T.-I.H. designed the study and wrote the paper. All authors approved the final version of the manuscript. Declaration of competing interest No competing interest. Research registration unique identifying number (UIN) 1. Name of the registry: NA. 2. Unique Identifying number or registration ID: NA. 3. Hyperlink to your specific registration (must be publicly accessible and will be checked): NA. Provenance and peer review Not commissioned, externally reviewed. Guarantor Teh-Ia Huo.